Pharmacological studies have suggested the presence of multiple opiate receptors. Scatchard analysis of opiate binding studies with a variety of radioactive opiate agonists and antagonists demonstrate two binding components with differing affinities for opiates. These high and low affinity binding components may play a role in explaining the pharmacological evidence for multiple opiate receptors. A variety of techniques known to affect opiate binding will be investigated to determine biochemical differences between the two affinity binding sites. Studies will then be continued with naloxazone, a long-acting opiate antagonist which blocks only high affinity binding in vivo. Blockade of these high affinity binding sites decreases morphine's analgetic potency over 10 fold without affecting the LD50. Further tests will be done to establish the pharmacological relevance of both classes of binding sites. Radioactively labelled naloxazone of high specific activity will also be used to investigate opiate receptor turnover in vivo and the biochemistry of solubilized receptors.